Tag Archive for: PET/CT in biochemical relapse of prostate cancer

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Article of the Month: Choline-PET/CT radical PCa treatment

Every Month the Editor-in-Chief selects the Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Clinical utility of 18F-fluorocholine positron-emission tomography/computed tomography (PET/CT) in biochemical relapse of prostate cancer after radical treatment: results of a multicentre study

Sonia Rodado-Marina, Mónica Coronado-Poggio, Ana María García-Vicente*,
Jose Ramón García-Garzón, Juan Carlos Alonso-Farto††, Aurora Crespo de la Jara‡, Antonio Maldonado-Suárez§ and Antonio Rodríguez-Fernández

 

Department of Nuclear Medicine, La Paz Universitary Hospital and §Quirón Universitary Hospital, Madrid, *Department of Nuclear Medicine, Universitary Hospital, Ciudad Real, CETIR Unitat PET Esplugues, Barcelona, ††Gregorio Marañón Universitary Hospital, Madrid, Department of Nuclear Medicine, Quirón Hospital, Torrevieja, and Department of Nuclear Medicine, Virgen de las Nieves Universitary Hospital, Granada, Spain

 

OBJECTIVE

To evaluate 18F-fluorocholine positron-emission tomography (PET)/computed tomography (CT) in restaging patients with a history of prostate adenocarcinoma who have biochemical relapse after early radical treatment, and to correlate the technique’s disease detection rate with a set of variables and clinical and pathological parameters.

PATIENTS AND METHODS

This was a retrospective multicentre study that included 374 patients referred for choline-PET/CT who had biochemical relapse. In all, 233 patients who met the following inclusion criteria were analysed: diagnosis of prostate cancer; early radical treatment; biochemical relapse; main clinical and pathological variables; and clinical, pathological and imaging data needed to validate the results. Criteria used to validate the PET/CT: findings from other imaging techniques, clinical follow-up, treatment response and histological analysis. Different statistical tests were used depending on the distribution of the data to correlate the results of the choline-PET/CT with qualitative [T stage, N stage, early radical prostatectomy (RP) vs other treatments, hormone therapy concomitant to choline-PET/CT] and quantitative [age, Gleason score, prostate-specific antigen (PSA) levels at diagnosis, PSA nadir, PSA level on the day of the choline-PET/CT (Trigger PSA) and PSA doubling time (PSADT)] variables. We analysed whether there were independent predictive factors associated with positive PET/CT results.

RESULTS

Choline-PET/CT was positive in 111 of 233 patients (detection rate 47.6%) and negative in 122 (52.4%). Disease locations: prostate or prostate bed in 26 patients (23.4%); regional and/or distant lymph nodes in 52 (46.8%); and metastatic bone disease in 33 (29.7%). Positive findings were validated by: results from other imaging techniques in 35 patients (15.0%); at least 6 months of clinical follow-up in 136 (58.4%); treatment response in 24 (10.3%); histological analysis of lesions in 17 (7.3%); and follow-up plus imaging results in 21 (9.0%). The statistical analysis of qualitative variables, corresponding to patients’ clinical characteristics, and the positive/negative final PET/CT results revealed that only whether or not early treatment with RP was done was statistically significant (P < 0.001), with the number of positive results higher in patients who did not undergo a RP. Among the quantitative variables, Gleason score, Trigger PSA and PSADT clearly differentiated the two patient groups (positive and negative choline-PET/CT: P = 0.010, P = 0.001 and P = 0.025, respectively). A Gleason score of <5 or ≥8 clearly differentiated positive from negative PET. Trigger PSA: mean of 8 ng/mL for positive PET/CT vs 2.8 ng/mL for negative PET/CT; PSADT: mean of 8 months for positive vs 12.6 months for negative. The optimal threshold values were: 3 ng/mL for Trigger PSA level and 6 months for PSADT (Youden index/receiver operating characteristic curve). Analysing these two variables together showed that PSADT was more conclusive in patients with lower Trigger PSA levels. Analysing variables by location showed that only PSADT was able to differentiate between those with disease confined to the prostate compared with the other two locations (lymph nodes and bone), with shorter PSADT in these two, which was statistically significant (P < 0.002). In the patient group with a PSA level of <1.5 ng/mL, 30.8% had the disease, 7% of whom had metastatic bone disease. In the multivariate logistic regression, the risks factors that were clearly independent for those with positive PET/CT were: PSA level of >3 ng/mL, no early RP, and Gleason score of ≥8.

CONCLUSIONS

Our results support the usefulness of 18F-fluorocholine PET/CT in biochemical relapse of prostate cancer after radical treatment, with an overall disease detection rate close to 50%, and it can be recommended as first-line treatment. As mentioned above, besides Trigger PSA levels, there are other clinical and pathological variables that need to be considered so as to screen patients properly and thus minimise the number of nodular lesions and increase the diagnostic accuracy of the examination.

Editorial: Choline-PET/CT in relapsing prostate cancer patients

18F-choline positron emission tomography (PET)/C T has become a modern imaging technique in men with prostate cancer and biochemical relapse after local treatment with curative intent (radical prostatectomy, external beam/intensity-modulated radiation therapy, brachytherapy) in order to differentiate between local, locoregional and systemic relapse. Although 18F-choline PET/CT will probably be replaced by prostate-specific membrane antigen-PET/CT in the near future, the present paper by Rodada-Marina et al. [1] is important for daily routine because the authors attempt to define the current role of 18F-choline PET/CT in the diagnostic algorithm of men with relapsing PSA and to define specific patient cohorts in whom 18F-choline PET/CT might have a significant impact in the decision-making process regarding the most appropriate treatment.

Two issues are important to me when discussing the potential indication for performing new imaging studies in my patients with relapsing PSA: (1) whether the method is sensitive enough to detect a metastatic deposit at a given PSA serum concentration and (2) whether a positive finding using this imaging method would change my treatment recommendation. In this context, the current recommendation is 18F-choline PET/CT at a PSA serum concentration >1 ng/mL if a therapeutic consequence will be drawn [2]. If the patient would not be a candidate for a secondary local treatment option, such as salvage radiation therapy or salvage radical prostatectomy, but he would be treated with androgen deprivation therapy anyhow, none of the modern imaging studies would make sense.

In the present paper, a total of 233 patients from six different institutions were included in a retrospective study. One of the most important findings of this paper is that the detection rate was only 47.6%, despite relatively high mean and median trigger PSA serum levels of 5.3 and 2.8 ng/mL, respectively. The detection rates varied between 23.5 and 38.2% in men with PSA serum levels between <1 and 2–3 ng/mL and the detection only increased to 67% in men with PSA levels ≥3 ng/mL. Moreover, the authors identified that the best threshold for the trigger PSA level was 3.5 ng/mL, with a sensitivity and a specificity of 64 and 76%, respectively. With regard to PSA doubling time (PSA-DT), the best threshold was < 6 months, with a sensitivity and a specificity of 58% only. Based on these very high PSA serum levels at the time of imaging studies, which had the potential intent to select the most appropriate therapy, the majority of patients were already beyond the scope of secondary local therapy with curative intent [2, 3]. Furthermore, it was shown that patients with a Gleason score 8–10 and a PSA-DT of <6 months have a higher probability of having systemic disease – a fact which is well known already.

What do these data mean for clinical practice? There might be three clinical scenarios in which imaging studies might exert a significant impact on further treatment: (1) salvage radiation therapy in men with PSA relapse after radical prostatectomy (RP) [2, 3], (2) salvage RP after radiation therapy of the prostate [4] and (3) salvage pelvic lymphadenectomy in men with PSA relapse after RP or radiation therapy of the prostate [5]. In my view, the data underline the fact that imaging with 18F-choline PET/CT is not helpful in the first clinical scenario, early or late PSA relapse after RP. The clinician needs to start local salvage therapy, such as percutaneous radiation therapy, at a serum PSA concentration well below 0.5 ng/mL if a curative intent is the focus of treatment [2, 3]. Based on the current data, only one fifth of the patient cohort had a positive 18F-choline PET/CT finding even when considering aggressive biological features such as a high Gleason score, a rapid PSA-DT and a high PSA nadir after RP; therefore, PET/CT does not add significant additional diagnostic information in the individual patient so that it does not appear useful to perform 18F-choline PET/CT in men with low PSA levels at time of relapse. 18F-choline PET/CT might be helpful in the second clinical scenario to identify patients who will benefit from salvage RP. It has been shown that a PSA < 10 ng/mL and a PSA-DT >12 months at time of surgery are the most significant prognosticators for identifying organ-confined disease [4]. A positive detection rate for metastatic foci would be >75% in this scenario, underlining the indication for performing choline PET/CT. With regard to the third clinical scenario, it has been shown that a serum PSA <4 ng/mL and a slow PSA-DT represent prognostic markers for selecting men who most probably have locoregional relapse in the small pelvis and who will benefit the most from salvage lymphadenectomy [5]. Again, choline-PET/CT is indicated to exclude retroperitoneal or systemic disease and it should be performed before any salvage procedure.

In conclusion, the retrospective study performed by Rodado-Marina et al. [1] provides significant and clinically useful information with regard to the definition of a patient cohort that would benefit most from the performance of a choline PET/CT. This information should be considered when counselling patients with regard to the need for new imaging methods at the time of PSA relapse.

Axel Heidenreich,

 

Department of Urology,Uniklinik RWTH University Aachen, Aachen, Germany

 

References

 

 

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